Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice
Meilin Wu, … , Joshua B. Plotkin, Jonathan A. Epstein
Meilin Wu, … , Joshua B. Plotkin, Jonathan A. Epstein
Published May 15, 2008
Citation Information: J Clin Invest. 2008;118(6):2076-2087. https://doi.org/10.1172/JCI33715.
View: Text | PDF
Research Article Development Article has an altmetric score of 3

Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice

  • Text
  • PDF
Abstract

Transcription factors regulate tissue patterning and cell fate determination during development; however, expression of early regulators frequently abates upon differentiation, suggesting that they may also play a role in maintaining an undifferentiated phenotype. The transcription factor paired box 3 (Pax3) is expressed by multipotent neural crest precursors and is implicated in neural crest disorders in humans such as Waardenburg syndrome. Pax3 is required for development of multiple neural crest lineages and for activation of lineage-specific programs, yet expression is generally extinguished once neural crest cells migrate from the dorsal neural tube and differentiate. Using a murine Cre-inducible system, we asked whether persistent Pax3 expression in neural crest derivatives would affect development or patterning. We found that persistent expression of Pax3 in cranial neural crest cells resulted in cleft palate, ocular defects, malformation of the sphenoid bone, and perinatal lethality. Furthermore, we demonstrated that Pax3 directly regulates expression of Sostdc1, a soluble inhibitor of bone morphogenetic protein (BMP) signaling. Persistent Pax3 expression renders the cranial crest resistant to BMP-induced osteogenesis. Thus, one mechanism by which Pax3 maintains the undifferentiated state of neural crest mesenchyme may be to block responsiveness to differentiation signals from the environment. These studies provide in vivo evidence for the importance of Pax3 downregulation during differentiation of multipotent neural crest precursors and cranial development.

Authors

Meilin Wu, Jun Li, Kurt A. Engleka, Bo Zhou, Min Min Lu, Joshua B. Plotkin, Jonathan A. Epstein

×

Total citations by year

Year: 2025 2024 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2010 2009 2008 Total
Citations: 1 2 2 1 4 4 3 2 5 3 4 3 2 1 2 3 42
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (42)

Title and authors Publication Year
Cleft Palate Induced by Mycophenolate Mofetil Is Associated with miR-4680-3p and let-7c-5p in Human Palate Cells
Yoshioka H, Horita H, Tsukiboshi Y, Kurita H, Ogata A, Ogata K
Non-Coding RNA 2025
Prevention and treatment of peri-implant fibrosis by functionally inhibiting skeletal cells expressing the leptin receptor.
Suhardi VJ, Oktarina A, Hammad M, Niu Y, Li Q, Thomson A, Lopez J, McCormick J, Ayturk UM, Greenblatt MB, Ivashkiv LB, Bostrom MPG, Yang X
Nature Biomedical Engineering 2024
A Pax3 lineage gives rise to transient haematopoietic progenitors
Canu G, Correra R, Diez-Pinel G, Castellan RF, Denti L, Fantin A, Ruhrberg C
Development (Cambridge, England) 2024
Pax3 Hypomorphs Reveal Hidden Pax7 Functional Genetic Compensation in Utero
Zhou HM, Conway SJ
Journal of Developmental Biology 2022
Downregulation of the paired box gene 3 inhibits the progression of skin cutaneous melanoma by inhibiting c-MET tyrosine kinase : PAX3 downregulation inhibits melanoma progression.
Zhang K, Yu C, Tian R, Zhang W, Tang S, Wang G
Molecular Biology Reports 2022
The Mandibular and Hyoid Arches—From Molecular Patterning to Shaping Bone and Cartilage
J Fabik, V Psutkova, O Machon
International journal of molecular sciences 2021
Chemical‐induced craniofacial anomalies caused by disruption of neural crest cell development in a zebrafish model
S Liu, R Narumi, N Ikeda, O Morita, J Tasaki
Developmental Dynamics 2020
Neural crest cells require Meis2 for patterning the mandibular arch via the Sonic hedgehog pathway
J Fabik, K Kovacova, Z Kozmik, O Machon
Biology Open 2020
The KMT2D Kabuki syndrome histone methylase controls neural crest cell differentiation and facial morphology
KB Shpargel, CL Mangini, G Xie, K Ge, T Magnuson
Development (Cambridge, England) 2020
Gone Caving: Roles of the Transcriptional Regulators YAP and TAZ in Skeletal Development
CD Kegelman, JM Collins, MP Nijsure, EA Eastburn, JD Boerckel
Current Osteoporosis Reports 2020
Mouse embryonic palatal mesenchymal cells maintain stemness through the PTEN-Akt-mTOR autophagic pathway
L Shi, B Li, B Zhang, C Zhen, J Zhou, S Tang
Stem Cell Research & Therapy 2019
The True Story of Yeti, the “Abominable” Heterochromatic Gene of Drosophila melanogaster
Y Prozzillo, FD Monache, D Ferreri, S Cuticone, P Dimitri, G Messina
Frontiers in physiology 2019
Emerging Pathogenic and Prognostic Significance of Paired Box 3 (PAX3) Protein in Adult Gliomas
E Angelopoulou, YN Paudel, C Piperi
Translational oncology 2019
Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction
KB Paiva, CS Maas, PM dos Santos, JM Granjeiro, A Letra
Frontiers in Cell and Developmental Biology 2019
Ectopic Hedgehog Signaling Causes Cleft Palate and Defective Osteogenesis
NL Hammond, KJ Brookes, MJ Dixon
Journal of dental research 2018
Ablation of Ezh2 in neural crest cells leads to aberrant enteric nervous system development in mice
H Kim, IM Langohr, M Faisal, M McNulty, C Thorn, J Kim, M Schubert
PloS one 2018
Association of low-frequency genetic variants in regulatory regions with nonsyndromic orofacial clefts
JR Shaffer, J LeClair, JC Carlson, E Feingold, CJ Buxó, K Christensen, FW Deleyiannis, LL Field, JT Hecht, L Moreno, IM Orioli, C Padilla, AR Vieira, GL Wehby, JC Murray, SM Weinberg, ML Marazita, EJ Leslie
American journal of medical genetics. Part A 2018
Hoxa2 Inhibits Bone Morphogenetic Protein Signaling during Osteogenic Differentiation of the Palatal Mesenchyme
PP Iyyanar, AJ Nazarali
Frontiers in physiology 2017
The human Cranio Facial Development Protein 1 (Cfdp1) gene encodes a protein required for the maintenance of higher-order chromatin organization
G Messina, MT Atterrato, Y Prozzillo, L Piacentini, A Losada, P Dimitri
Scientific Reports 2017
Restricted Pax3 Deletion within the Neural Tube Results in Congenital Hydrocephalus
HM Zhou, S Conway
Journal of Developmental Biology 2016
Actin capping protein CAPZB regulates cell morphology, differentiation, and neural crest migration in craniofacial morphogenesis
K Mukherjee, K Ishii, V Pillalamarri, T Kammin, JF Atkin, SE Hickey, QJ Xi, CJ Zepeda, JF Gusella, ME Talkowski, CC Morton, RL Maas, EC Liao
Human Molecular Genetics 2016
Mutations and altered expression of SERPINF1 in patients with familial otosclerosis
JL Ziff, M Crompton, HR Powell, JA Lavy, CP Aldren, KP Steel, SR Saeed, SJ Dawson
Human Molecular Genetics 2016
Expression of human Cfdp1 gene in Drosophila reveals new insights into the function of the evolutionarily conserved BCNT protein family
G Messina, MT Atterrato, L Fanti, E Giordano, P Dimitri
Scientific Reports 2016
Waardenburg syndrome type I: Dental phenotypes and genetic analysis of an extended family
Sólia-Nasser L, de Aquino SN, Paranaíba LM, Gomes A, dos-Santos-Neto P, Coletta RD, Cardoso AF, Frota AC, Martelli-Júnior H
Medicina Oral, Patología Oral y Cirugía Bucal 2016
Ly6h Regulates Trafficking of Alpha7 Nicotinic Acetylcholine Receptors and Nicotine-Induced Potentiation of Glutamatergic Signaling
CA Puddifoot, M Wu, RJ Sung, WJ Joiner
The Journal of neuroscience : the official journal of the Society for Neuroscience 2015
Receptor tyrosine kinases modulate distinct transcriptional programs by differential usage of intracellular pathways: ( A ) Mouse embryonic palatal mesenchyme (MEPM) cells were dissected from E13.5 embryos, passaged twice, and then serum starved overnight prior to stimulation with either PDGFAA or FGF1 + heparin. ( B ) Expression of all genes with FPKM (fragments per kilobase of exon per million reads mapped) >1 at 1 hr (11,217 genes) and ( B' ) 4 hr (11,266 genes). Genes colored blue are significantly increased with fibroblast growth factor (FGF) treatment and genes colored red are significantly increased with platelet-derived growth factor (PDGF) treatment. Values plotted on log 2 scale. ( C ) Fold change (FC) comparison for all differentially expressed (DE) genes at ( C ) 1 hr or ( C' ) 4 hr (compared to serum starved sample) shows high correlation between the transcriptional response to each growth factor at 1 hr but low correlation at 4 hr. ( D ) Protein–protein interaction (PPI) network for all genes upregulated at 1 hr contains many classic immediate early genes (such as AP-1 components, Myc , and Srf ). Genes are colored based on their primary reported role in transcriptional regulation (22, 23), with orange squares representing activators and gray circles representing repressors. ( E ) FC (compared to untreated sample) for selected genes upregulated at 1 hr. Genes in bold are induced >1.5-fold in response to the indicated growth factor. Although both PDGF and FGF regulate many shared targets, the induction in response to FGF exhibits greater magnitude ( Fos , Fosb , Junb , Atf3 , Egr1 , Egr2 ) and longer duration ( Fos , Fosb , Jun , Junb , Egr1 , Egr2 )
HN Vasudevan, P Mazot, F He, P Soriano
eLife 2015
Mechanisms of Inhibition and Potentiation of α4β2 Nicotinic Acetylcholine Receptors by Members of the Ly6 Protein Family
M Wu, CA Puddifoot, P Taylor, WJ Joiner
The Journal of biological chemistry 2015
SLEEPLESS Is a Bifunctional Regulator of Excitability and Cholinergic Synaptic Transmission
M Wu, JE Robinson, WJ Joiner
Current Biology 2014
Heritability of Craniofacial Structures in Normal Subjects and Patients with Sleep Apnea
L Chi, FL Comyn, BT Keenan, J Cater, G Maislin, AI Pack, RJ Schwab
Sleep 2014
Pax3 isoforms in sensory neurogenesis: Expression and function in the ophthalmic trigeminal placode: Pax3 Isoforms in Sensory Neurogenesis
JS Adams, SN Sudweeks, MR Stark
Developmental Dynamics 2014
The Bucentaur (BCNT) protein family: a long-neglected class of essential proteins required for chromatin/chromosome organization and function.
Messina G, Celauro E, Atterrato MT, Giordano E, Iwashita S, Dimitri P
Chromosoma 2014
Identification of candidate downstream targets of TGFβ signaling during palate development by genome-wide transcript profiling
RC Pelikan, J Iwata, A Suzuki, Y Chai, JG Hacia
Journal of Cellular Biochemistry 2013
Murine craniofacial development requires Hdac3-mediated repression of Msx gene expression
N Singh, M Gupta, CM Trivedi, MK Singh, L Li, JA Epstein
Developmental Biology 2013
 -catenin regulates Pax3 and Cdx2 for caudal neural tube closure and elongation
T Zhao, Q Gan, A Stokes, RN Lassiter, Y Wang, J Chan, JX Han, DE Pleasure, JA Epstein, CJ Zhou
Development (Cambridge, England) 2013
A genome-wide association study identifies five loci influencing facial morphology in Europeans
F Liu, F der Lijn, C Schurmann, G Zhu, MM Chakravarty, PG Hysi, A Wollstein, O Lao, M Bruijne, MA Ikram, A der Lugt, F Rivadeneira, AG Uitterlinden, A Hofman, WJ Niessen, G Homuth, G Zubicaray, KL McMahon, PM Thompson, A Daboul, R Puls, K Hegenscheid, L Bevan, Z Pausova, SE Medland, GW Montgomery, MJ Wright, C Wicking, S Boehringer, TD Spector, T Paus, NG Martin, R Biffar, M Kayser
PLoS genetics 2012
Clinical significance and prognostic value of PAX3 expression in human glioma.
Chen J, Xia L, Wu X, Xu L, Nie D, Shi J, Xu X, Ni L, Ju S, Wu X, Zhu H, Shi W
Journal of molecular neuroscience : MN 2012
Arginylation-dependent neural crest cell migration is essential for mouse development
S Kurosaka, NA Leu, F Zhang, R Bunte, S Saha, J Wang, C Guo, W He, A Kashina
PLoS genetics 2010
Quantitative trait loci, genes, and polymorphisms that regulate bone mineral density in mouse
Q Xiong, Y Jiao, KA Hasty, ST Canale, JM Stuart, WG Beamer, HW Deng, D Baylink, W Gu
Genomics 2009
Novel Regulators of Fgf23 Expression and Mineralization in Hyp Bone
S Liu, W Tang, J Fang, J Ren, H Li, Z Xiao, LD Quarles
Molecular Endocrinology 2009
Pigmentation PAX-ways: the role of Pax3 in melanogenesis, melanocyte stem cell maintenance, and disease
JD Kubic, KP Young, RS Plummer, AE Ludvik, D Lang
Pigment Cell & Melanoma Research 2008
Activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the ophthalmic trigeminal placode
CM Dude, CY Kuan, JR Bradshaw, ND Greene, F Relaix, MR Stark, CV Baker
Developmental Biology 2008
Activation of Pax3 target genes is necessary but not sufficient for neurogenesis in the ophthalmic trigeminal placode.
Dude CM, Kuan CY, Bradshaw JR, Greene ND, Relaix F, Stark MR, Baker CV
Developmental Biology 2008

← Previous 1 2 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 2 Wikipedia pages
73 readers on Mendeley
See more details